Cigarette smoke and glutathione: Focus on in vitro cell models. (June 2020)

• Record Type: Journal Article
• Authors: Dalle-Donne, Isabella; Garavaglia, Maria L.; Colombo, Graziano; Astori, Emanuela; Lionetti, Maria C.; La Porta, Caterina A.M.; Santucci, Annalisa; Rossi, Ranieri; Giustarini, Daniela; Milzani, Aldo
• Is Part Of: Toxicology in vitro. Volume 65(2020)
• Publication Date: 2020-06
• Subjects: Cigarette smoke -- Glutathione -- in vitro cell models -- Oxidative stress -- Smokers -- Oxidative damage; (CyS)2 cystine -- 4-HNE 4-hydroxy-2-nonenal -- ABCC ATP-binding cassette subfamily C proteins -- ALI air-liquid-interface -- CFTR cystic fibrosis transmembrane regulator protein -- CS cigarette smoke -- CSC cigarette smoke condensate -- CSE cigarette smoke extract -- Cys cysteine -- ELF epithelial lining fluid -- GCL glutamate cysteine ligase (also called γ-glutamylcysteine synthetase, γ-GCS) -- GCLC glutamate cysteine ligase, catalytic subunit -- GCLM glutamate cysteine ligase, modulatory subunit -- GGT γ-glutamyltranspeptidase (also called γ-glutamyl transferase, γGT) -- Glu glutamic acid/glutamate -- Gly glycine -- GPx glutathione peroxidase -- GR glutathione reductase -- Grx glutaredoxin (also called thioltransferase) -- GS glutathione synthetase -- GSH glutathione -- GSSG glutathione disulphide -- GST glutathione-S-transferase -- MRP multidrug-associated resistance proteins -- NADPH nicotinamide adenine dinucleotide phosphate -- PSSG S-glutathionylated proteins -- ROS reactive oxygen species; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.104818
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Cigarette smoke (CS) is one of the most important preventable risk factors for the development of respiratory diseases, cardiovascular diseases, stroke, and various types of cancer. Due to its high intracellular concentration and central role in maintaining the cellular redox state, glutathione (GSH) is one of the key players in several enzymatic and non-enzymatic reactions necessary for protecting cells against CS-induced oxidative stress. A plethora of in vitro cell models have been used over the years to assess the effects of CS on intracellular GSH and its disulphide forms, i.e. glutathione disulphide (GSSG) and S -glutathionylated proteins. In this review, we described the effects of cell exposure to CS on cellular GSH and formation of its oxidized forms and adducts (GSH-conjugates). We also discussed the limitations and relevance of in vitro cell models of exposure to CS and critically assessed the congruence between smokers and in vitro cell models. What emerges clearly is that results obtained in vitro should be interpreted with extreme caution, bearing in mind the limitations of the specific cell model used. Despite this, in vitro cell models remain important tools in the assessment of CS-induced oxidative damage. Highlights: GSH protects cells against cigarette smoke (CS)-induced oxidative stress. Effects of CS on GSH and its disulphides in several human cell models are described. We discussed the limitations and relevance of cell models of exposure to CS. We also critically assessed the congruence between smokers and in vitro cell models.